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Biomedical subjects

E Jones

Publications and source records attributed to E Jones.

At least 19 recordsLinked to original sources

A recombinant sporozoite surface antigen of Theileria parva induces protection in cattle.

At present immunization against Theileria parva is by infection with live sporozoites and simultaneous treatment with a long-acting oxytetracycline. This method has major limitations in that live organisms are used and the immunity engendered is parasite stock specific. In an attempt to develop an alternative immunization procedure, the gene encoding p67, a major surface antigen of sporozoites, has been expressed by using the plasmid expression vector pMG1. The gene, which has been characterized previously, encodes 709 amino acid residues, contains a single intron of 29 base pairs, and is only transcribed during sporogony. The recombinant p67 sequences were fused to the first 85 amino acid residues derived from a nonstructural gene (NS1) of influenza virus A. Immunization with a partially purified recombinant antigen emulsified in 3% saponin induced sporozoite neutralizing antibodies in cattle and provided protection in six of nine animals on homologous challenge with T. parva sporozoites. This recombinant antigen is therefore a candidate for development of a vaccine against T. parva.

Animals

Absence of mutagenic activity in Salmonella and of clastogenic activity in CHO cells of Caramel Colours I, II, III and IV.

A total of 15 caramel colours were examined for genotoxic activity using the Salmonella typhimurium plate incorporation assay (Ames test). Five bacterial strains, TA1535, TA1537, TA1538, TA98 and TA100 were used in all the plate incorporation tests. Caramel colours can be divided into four classes, classification depending on the preparative method used. In this study, representatives of all four classes of caramel colour were tested for genotoxic potential in the Ames test, some of the caramel colours being tested both with and without a pre-incubation stage. None of the 15 caramel colours tested exhibited genotoxic potential in any of the five bacterial tester strains. The last two caramel colours tested, in the series of 15 [203-23-4 (Class II) and 311 (Class III)] were also assessed for clastogenic potential. For this test, cultures of CHO cells were exposed to the two caramel colours and metaphase preparations from these cultures examined for evidence of chromosomal aberrations. No evidence of chromosome damaging activity was observed.

Animals

Assessment of the genotoxic potential of Caramel Colour I in four short-term tests.

A battery of three short-term tests in vitro and one in vivo was used to determine the genotoxicity of Caramel Colour I. The results of the bacterial mutation assay, using five strains of Salmonella typhimurium, and the mouse micronucleus assay in vivo showed no evidence of genotoxic activity. Results from both the cytogenetics assay in vitro, using CHO cells, and the mouse lymphoma assay indicated that there was some genotoxic activity associated with Caramel Colour I but only in the absence of S-9 and at very high dose levels.

Animals

Quality of life of patients treated surgically for head and neck cancer.

The quality of survival of 48 patients treated surgically for head and neck cancer was assessed using a problem-orientated self-administered questionnaire. The questionnaire was based on the European Organization for Research into the Treatment of Cancer (EORTC) core questionnaire to which a specific head and neck module was added. The following domains were studied: pain, fatigue, physical symptoms (gastrointestinal and 'other'), functional activity, psychological symptoms, overall physical condition and overall quality of life. For the analysis, five groups of patients were considered: laryngectomy (n = 15), pharyngolaryngoesophagectomy (n = 5), craniofacial procedure (n = 11), 'other operations' (n = 9) and patients with disease recurrence (n = 8). Each group identified different problem areas. Laryngectomees and 'other operation' patients reported relatively few problems, whereas patients with disease recurrence described difficulties in all of the domains examined. Symptoms of fatigue were common. Information collected in this way may facilitate improved rehabilitation and thus better quality of survival.

Adult

Comparison and interaction of low dose felodipine and enalapril in the treatment of essential hypertension in elderly subjects.

The antihypertensive effect and tolerance of the combined low doses of felodipine and enalapril (5 + 5 mg daily) were compared with those of either drug at a higher dose level (10 mg daily). Our double-blind, three-way crossover study (balanced Latin square design) involved 36 elderly subjects (mean age 67 +/- 6 years) with essential hypertension. After a 4-week placebo run-in phase the subjects were randomized to the active treatment periods, starting with 5 mg felodipine plus 5 mg enalapril, 5 mg felodipine, or 5 mg enalapril daily for the first 4 weeks. The doses in the felodipine and enalapril periods were then doubled for another 2 weeks. All medication was given once daily in the morning, and blood pressure was measured 24 h after a previous dose. The supine blood pressure for subjects given placebo was 178/101 mm Hg. After 6 weeks' treatment systolic and diastolic supine blood pressures were significantly lower with 5 mg felodipine plus 5 mg enalapril (154/85 mg Hg) than with 10 mg felodipine (159/88 mm Hg) or with 10 mg enalapril (162/91 mm Hg), and the diastolic blood pressure was significantly lower with felodipine than with enalapril. At the end of the felodipine plus enalapril, felodipine, and enalapril treatment periods, 75, 69, and 56% of the subjects, respectively, had a supine diastolic blood pressure 90 mm Hg or less. The combination was tolerated better than either monotherapy. The most commonly reported adverse event was swollen ankles, which occurred in one, nine, and five subjects during felodipine plus enalapril, felodipine, and enalapril treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

In vivo imaging of insulin receptors in monkeys using 18F-labeled insulin and positron emission tomography.

We previously described a prosthetic group methodology for incorporating 18F into peptides and showed that 18F-labeled insulin (18F-insulin) binds to insulin receptors on human cells (IM-9 lymphoblastoid cells) with affinity equal to that of native insulin (1). We now report studies using 18F-insulin with positron emission tomography to study binding to insulin receptors in vivo. Positron emission tomography scans were performed in six rhesus monkeys injected with 0.3-1.4 mCi of 18F-insulin (approximately 0.1 nmol, SA 4-11 Ci/mumol). Integrity of the tracer in blood, determined by immunoprecipitation, was 94% of control for the first 5 min and decreased to 31% by 30 min. Specific, saturable uptake of 18F was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, approximately 1 nmol) with the 18F-insulin reduced liver and increased kidney uptake of the labeled insulin. Liver radioactivity was decreased by administration of unlabeled insulin at 3 min, but not 5 min, after administration of the tracer, while some kidney radioactivity could be displaced 5 min after injection. Clearance of 18F was predominantly in bile and urine. 18F-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney.

Animals

Cognitive impairment in patients with systemic lupus erythematosus.

Seventy unselected patients with systemic lupus erythematosus (SLE) were studied to determine the prevalence of cognitive impairment and the association with other clinical variables. Twenty-five patients with rheumatoid arthritis (RA) and 23 healthy subjects were used as controls. All patients were evaluated with a battery of standardized neuropsychological tests to determine ability in 8 areas of cognitive function. Clinically overt neuropsychiatric (NP) SLE, cumulative disease manifestations and concurrent medications were documented. In patients with SLE, generalized disease activity was expressed using the SLE disease activity index. Cognitive impairment was identified in 15/70 (21%) patients with SLE, 1/25 (4%) patients with RA and in 1/23 (4%) healthy subjects (p = 0.042). The prevalence was higher in patients with active NP-SLE at the time of assessment (2/5, 40%) compared to patients with inactive NP-SLE (2/10, 20%) but was also increased in those patients who had never had known clinical NP-SLE (11/55, 20%). A history of serositis (p = 0.015), active SLE (p = 0.064) and corticosteroid use (p = 0.027) at the time of assessment were more common in patients with cognitive impairment. The results suggest that cognitive impairment is increased in patients with SLE. It may occur independently of clinically overt NP-SLE and is more common in patients with active disease who are receiving corticosteroids.

Adult

Loss of sexual dimorphism in rat arcuate nucleus neuronal membranes with reproductive aging.

Arcuate neurons of the rat hypothalamus have a sexual dimorphic membrane phenotype: quantitative analysis of freeze-fracture replicas has revealed that a population of intramembrane protein particles (IMP) of small size (less than 10 nm) is enriched in the plasma membrane of perikarya and dendritic shafts of cycling females compared to males, whereas a population of large IMPs (greater than 10 nm) is enriched in the membrane of dendritic shafts of males. This different membrane organization is associated with a sex dimorphic synaptic connectivity. To determine whether sex differences in neuronal membrane are affected by reproductive senescence, IMPs were assessed in freeze-fracture replicas of arcuate neuronal plasma membranes of male and female Sprague-Dawley rats aged 3, 15, and 18 months. Three-month-old cycling females were studied on the morning of estrus. Senescent females were in constant estrus (15 months old) or in constant diestrus (18 months old). Young females had more IMPs with diameters under 10 nm in the inner and outer leaflets of the plasma membrane of the perikarya and dendritic shafts compared to males of the same age. In addition, young males showed an increased number of large (greater than 10 nm) IMPs in the outer membrane leaflet of dendritic shafts. No sex differences were detected in the membrane of dendritic spines. In senescent females the number of small IMPs was decreased in the perikarya and dendritic shafts compared to young females while the number of large particles was increased in the outer leaflet of the membrane of dendritic shafts, reaching values similar to those observed in males. IMP counts were not modified with aging in males and in dendritic spines of females. These results indicate that reproductive aging in female rats is associated with a remodeling of neuronal plasma membranes in arcuate neurons.

Aging

Frequency and intensity effects upon temporal and aerodynamic aspects of vocal fold diadochokinesis.

The present study of vocal fold diadochokinesis in 18 young adult women yielded statistically significant differences in intensity (at percentiles 25%, 50%, 75% of range) of production for vowel /lambda/ repetition rate. In addition, there were statistically significant differences for vocal frequency and intensity effects for airflow rate through the vocal folds at the 25th, 50th, and 75th percentile points within the functional vocal range. Clinical applications of the data are suggested.

Adult

Mechanisms of attentional selection: temporally modulated priority tags.

When a single abrupt onset appears in a multielement display, it captures attention. When multiple onset elements occur, they have conditional priority over no-onset elements such that a limited number of onsets can be serviced with high priority in visual search (Yantis & Johnson, 1990). We report three experiments in which we assess two possible mechanisms for attentional prioritization: a priority queue into which a fixed number of high-priority elements are placed for early servicing during search, and a mechanism that temporarily tags all high-priority elements for early servicing or more frequent sampling. We manipulated the visual quality or inter-letter confusability of the stimuli to prolong encoding and/or comparison operations; this manipulation led to a decrease in the estimated number of elements serviced with high priority. We conclude that a mechanism incorporating temporally decaying priority tags is implicated in servicing multiple abrupt onsets in visual search.

Adult

Response to sulfasalazine in rheumatoid arthritis: life table analysis of a 5-year followup.

Eighty-six patients with rheumatoid arthritis treated with sulfasalazine were followed for 5 years, or until treatment was discontinued. At the end of 5 years, there was a 22% probability of successfully continuing treatment. Most adverse effects developed in the first 3 months of treatment. In 38 patients treatment was discontinued because of inefficacy. In 18 of these, a brief period of improvement was followed by clinical relapse. Twenty were regarded as having no useful response to sulfasalazine. The treatment continuation rate of 22% at 5 years is in marked contrast to the pessimistic longterm evaluations of second line drugs that have recently been reported.

Adolescent

Strength and function in the normal and rheumatoid hand.

We have reevaluated the Martin vigorimeter to measure grip strength in healthy subjects, and patients with rheumatoid arthritis (RA), and investigated the correlation of grip strength and hand function using the Jebsen hand function tests and Purdue pegboard test before and after treatment. The vigorimeter showed good test-retest reliability (r greater than 0.911) and interrater reliability (r greater than 0.915). Test-retest reliability was greater than 0.97 for the Jebsen test, and greater than 0.94 for the Purdue test in healthy individuals. Seventeen patients with RA were studied at intervals of 1 to 16 weeks. Active joint count and grip strength both improved significantly. Improvement in grip strength correlated with improvement in active joint count. Hand function tests were significantly impaired in the patients with RA.

Adolescent

Children's self-assessment of performance and task-related help seeking.

The present research examined the role of self-assessment of performance on children's use of help-seeking as an achievement strategy. In two experiments, third- and fifth-grade children were blocked into low and high verbal skill groups. Children performed a multitrial verbal task in which they were required to indicate their confidence in the correctness of their tentative solution and then were given the opportunity to seek help before providing a final solution on each trial. The second experiment differed from the first in that subjects were provided with a common motivation for seeking help. Subjects' confidence in the correctness of their solution was found to influence both the frequency and type of help sought. High task-related skill was associated with the discriminating use of help-seeking as an achievement strategy, especially among boys. Also, both the frequency and type of help sought varied with self-assessments for older children more than for younger children. Findings are discussed in terms of grade and sex differences in the use of internally based cues for performance evaluation. The importance of accounting for the interplay of children's age and task specific skill with achievement-related goals is stressed.

Achievement

Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas.

Cutaneous sarcoidosis often responds poorly to topical and intralesional corticosteroids but may respond to moderate to high doses of oral corticosteroids. To avoid the use of systemic corticosteroids, we treated 17 patients with cutaneous sarcoidal granulomas with hydroxychloroquine (2 to 3 mg/kg/day) in an open clinical trial. If response occurred, other medications were first tapered and then the hydroxychloroquine dosage was reduced or stopped. The cutaneous lesions of 12 patients regressed within 4 to 12 weeks, and they were able to stop other therapies; three patients had a partial response, and two patients had no regression. Two of eight patients with pulmonary sarcoidosis improved. No ocular toxicity was noted.

Adult

Rare HRAS alleles and susceptibility to human breast cancer.

The suggestion that inherited rare alleles at the HRAS oncogene locus might be associated with susceptibility to breast cancer led us to test linkage of HRAS and the neighboring region of 11p15 to breast cancer susceptibility in 12 high-risk families. Linkage could be excluded within 17 cM of HRAS; the lod score for close linkage to HRAS was -19.9. In addition, rare HRAS alleles segregated independently of breast cancer in 8 families in which both occurred. Among unrelated breast cancer patients not selected for family history, rare HRAS alleles were slightly, but not significantly, more frequent than among controls (0.11 vs 0.04, P = 0.11). The HRAS region of 11p is not the site of a primary alteration leading to breast cancer.

Alleles

Prevalence of left ventricular hypertrophy in elderly patients with well controlled hypertension.

1. Left ventricular hypertrophy (LVH) was measured by echocardiography in 154 patients, mostly males, aged 55 years or more, with hypertension who had been well controlled for at least 2 years. 2. Satisfactory studies with no other cardiac lesions were available for 103 patients; 52% had LVH and 48% had normal left ventricular dimensions. 3. In patients with well controlled hypertension there was a high prevalence of LVH despite adequate control for at least 2 years. Neither the level of control nor the drugs used appeared to predict the outcome. 4. Consideration needs to be given to earlier treatment, greater lowering of blood pressure, or different drugs to reduce this high prevalence of LVH.

Aged